What is the most likely cause of alopecia associated with prolonged Total Parenteral Nutrition (TPN)?

Alopecia in Prolonged Total Parenteral Nutrition is Most Commonly Caused by Zinc Deficiency

Zinc deficiency is the most likely cause of alopecia associated with prolonged Total Parenteral Nutrition (TPN). 1, 2

Micronutrient Deficiencies in TPN-Associated Hair Loss

Zinc Deficiency

• Zinc deficiency is the most frequently suspected deficiency in TPN-associated hair loss, with rapid clinical responses reported from zinc therapy 3
• Studies have documented cases where plasma zinc levels fell to very low levels during long-term TPN, resulting in a syndrome characterized by dermatitis, alopecia, and enterocolitis 1
• The characteristic skin lesions of zinc deficiency resemble seborrheic dermatitis, occurring in areas with high sebaceous gland concentration, along with hyperkeratotic lesions on extensor surfaces of large joints 2
• These skin manifestations and alopecia resolve when serum zinc levels are raised above 60 μg/dL with appropriate zinc sulfate replacement 2

Other Potential Causes

Biotin Deficiency

• Biotin deficiency can also cause alopecia in TPN patients, particularly when no preformed biotin is provided and intestinal microbial biosynthesis is compromised 4
• Patients with biotin deficiency may present with alopecia totalis, hypotonia, and developmental delay 5
• However, biotin deficiency has become less common since biotin has been routinely added to TPN formulations 3

Essential Fatty Acid Deficiency

• Historically, essential fatty acid deficiency was associated with alopecia in TPN patients
• However, this has been largely eliminated by the regular use of lipid-containing parenteral nutrition 3

Selenium Deficiency

• Some cases of alopecia in infants on TPN have been relieved within weeks by selenium supplementation 3
• However, selenium deficiency is less commonly associated with alopecia compared to zinc deficiency

Diagnostic Approach for TPN-Associated Alopecia

1. Check serum zinc levels - primary investigation given the strong association with alopecia
2. Monitor copper levels when supplementing zinc, as they compete for absorption 6
3. Assess biotin status - through urinary biotin excretion and organic acid analysis 5
4. Evaluate essential fatty acid status - through triene/tetraene ratios 5
5. Consider selenium levels - particularly in patients with other symptoms like chronic diarrhea or unexplained anemia 6

Treatment Recommendations

• For zinc deficiency: Provide zinc sulfate supplementation to maintain serum zinc levels above 60 μg/dL 2
• For biotin deficiency: Administer biotin supplementation (100 μg/day has been shown effective; higher initial doses may be needed in severe cases) 5, 4
• For essential fatty acids: Ensure regular inclusion of lipid-containing TPN 3
• For selenium deficiency: Provide selenium supplementation as selenite 3

Clinical Pearls and Pitfalls

• Plasma biotin concentration may not accurately reflect biotin status in all cases 5
• The currently recommended biotin supplement for pediatric patients (20 μg/day) may be inadequate for treating biotin deficiency or maintaining normal biotin status during TPN 5
• Zinc deficiency symptoms may be more pronounced during anabolic phases when tissue demand for zinc increases 1
• When supplementing zinc, always monitor copper levels as they compete for absorption 6
• Micronutrient status is infrequently monitored in TPN patients, which may lead to undiagnosed deficiencies manifesting as hair loss 3

Based on the available evidence, zinc deficiency is the most common and well-documented cause of alopecia in patients receiving prolonged TPN, with characteristic skin manifestations and rapid response to zinc supplementation.